A natural theaflavins preparation inhibits HIV-1 infection by targeting the entry step: Potential applications for preventing HIV-1 infection
A natural theaflavins preparation inhibits HIV-1 infection by targeting the entry step: Potential applications for preventing HIV-1 infection
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天然茶黄素制剂通过靶向进入步骤抑制 HIV-1 感染：预防 HIV-1 感染的潜在应用
DOI：
10.1016/j.fitote.2011.11.016
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发表时间：
2012-03-01
期刊：
影响因子：
3.4
通讯作者：
Liu, Shuwen
中科院分区：
文献类型：
--
作者：
Yang, Jie;Li, Lin;Liu, Shuwen
茶黄素是冲泡红茶中茶多酚的主要成分。我们之前曾报道，茶黄素衍生物，如TF3，通过靶向gp41来抑制HIV-1的入侵。然而，茶黄素的分离纯化比较困难，且纯化后的化合物极不稳定。为了开发出经济实惠的抗HIV-1微晶来预防HIV的性传播，我们打算使用一种含有90%茶黄素的经济的天然制剂(TFMix)。用p24产生和荧光素酶活性检测其对HIV-1毒株的体外抗病毒活性。通过添加时间、细胞-细胞融合和生物物理方法研究了TFMix抑制HIV-1感染的机制。这些数据表明，TFMix对实验室适应株和原代HIV-1毒株具有较强的抗HIV-1活性，IC50<1.20µM，并能有效抑制T-20耐药HIV-1毒株的感染。机制研究表明，TFMix主要通过靶向gp41来抑制HIV-1的侵入，因为它有效地抑制了gp41六螺旋束(6-Hb)的形成和HIV-1包膜蛋白介导的细胞-细胞融合。TFMix也能抑制HIV-1逆转录酶(RT)的活性，但IC50约为抑制gp41 6-Hb形成的8倍，提示RT不是TFMix的主要靶点。总之，TFMix是一种经济的天然产品，含有高含量的茶黄素，通过破坏gp41 6-Hb核心结构靶向病毒进入步骤，具有强大的抗HIV-1活性。它有可能被开发成一种安全和负担得起的局部杀微生物剂，用于预防艾滋病毒的性传播。(C)2011爱思唯尔B.V.保留所有权利。
Theaflavins are the major components of tea polyphenols in brewed black tea. We previously reported that theaflavin derivatives, such as TF3, inhibited HIV-1 entry by targeting gp41. However, it is difficult to purify the individual theaflavins and the purified compounds are highly unstable. To develop theaflavins as affordable anti-HIV-1 microbide for preventing HIV sexual transmission, we intended to use an economic natural preparation containing 90% of theaflavins (TFmix). Its antiviral activity against HIV-1 strains was evaluated in vitro using p24 production and luciferase assays. The mechanism by which TFmix inhibits HIV-1 infection was investigated using time-of-addition, cell-cell fusion and biophysical assays. The data suggested TFmix exhibited potent anti-HIV-1 activity on lab-adapted and primary HIV-1 strains with IC50 less than 1.20 mu M. It also effectively inhibited infection by T-20 resistant HIV-1 strains. The mechanism studies suggest that TFmix mainly inhibit the HIV-1 entry by targeting gp41 since it is effective in inhibiting gp41 six-helix bundle (6-HB) formation and HIV-1 envelope protein-mediated cell-cell fusion. TFmix could also inhibit HIV-1 reverse transcriptase (RT) activity, but the IC50 is about 8-fold higher than that for inhibiting gp41 6-HB formation, suggesting RT is not a major target for TFmix. In conclusion, TFmix is an economic natural product preparation containing high content of theaflavins with potent anti-HIV-1 activity by targeting the viral entry step through the disruption of gp41 6-HB core structure. It has a potential to be developed as a safe and affordable topical microbicide for preventing sexual transmission of HIV. (C) 2011 Elsevier B.V. All rights reserved.